Dermatomyositis and systemic lupus erythematosus are autoimmune disorders of uncertain cause and without specific medical therapy, generally treated with non-specific immunosuppressive medications that have significant complications. We have studied muscle and blood samples from patients with dermatomyositis and other inflammatory myopathies, and believe that overproduction of interferon alpha and beta (IFN-a/b) by plasmacytoid dendritic cells is responsible for tissue injury in dermatomyositis specifically. Other investigators studying systemic lupus erythematosus (SLE) have also hypothesized that such overproduction of IFN-a/b is in part responsible for the manifestations of that disease. We propose to use high-throughput drug discovery methods to identify compounds of predicted efficacy for DM and SLE. Development of such compounds into safe and effective drugs for the treatment of DM and SLE is the long-term objective of this work.